Development of a Sustainable Catalytic Ester Amidation Process

Abstract

We describe the development of a sustainable ester amidation process. Base and solvent screening, combined with the application of Design of Experiments methodology was employed to identify an optimized set of reaction conditions using a sustainable protocol. Utilizing these optimized conditions, treatment of a range of ester derivatives with amino alcohols in the presence of a catalytic quantity of an K 3 PO 4 deploying iso-propanol as solvent results in the highly efficient generation of a range of amido-alcohol derivatives in good to excellent yield, accompanied with excellent Reaction Mass Efficiency (RME).

Cyclopentyl Methyl Ether: An Elective Ecofriendly Ethereal Solvent in Classical and Modern Organic Chemistry

“…It is, therefore, notable that MeOH/CPME solventm ixtures offer considerable potential asareplacement of similar MeOH/ CH 2 Cl 2 binary eluents within the chromatographic purification of al arges et of compounds of interesti nm edicinal chemistry. [121] Successful application of the same solventm ixtures to the resolution of enantiomersb ys upercritical fluid chromatography on chiral stationaryp hases has also been described. [122] Finally, CPME has been indicatedt ob ea ne ffective alternative to CHCl 3 in the liquid-phase chromatography of lipids.…”

A Heterogeneous Niobium(V) Oxide Catalyst for the Direct Amidation of Esters

“…To overcome these problems, homogeneous catalytic methods4–8 have also been developed for the amidation of esters with amines but the reported methods suffer from drawbacks, including limited substrate scope, high catalyst loading (>10 mol % with respect to substrate), and the need for additives. For example, catalytic methods with N‐heterocyclic carbenes,4a K 3 PO 4 ,4b and organobase4c, d tolerate only amino alcohols as amines. Although Sb(OEt) 3 ,5a Zr(O t Bu) 4 ,5b and triazabicyclo[4.4.0]dec‐5‐ene5c are effective homogeneous catalysts for the amidation of esters with various amines, these systems require high catalyst loading (10–30 mol %).…”

Heterobimetallic Lanthanide–Sodium Alkoxides Catalyze the Amidation of Esters

“…In comparison, the amide 3z formed in only 68 %y ield if 2equivalents of morpholine reactedw ith benzyl benzoate catalyzed by Ru-MACHO catalyst. [23] Furthermore, if 2-aminoethanol (2ab)w as treated with 1a,ag ood yield of 99 %w as obtained, and higher reactivitya nd chemoselectivity (amine vs. alcohol) than that of some organobase-catalyzed systems [9,16] was observed, with the free hydroxy group not interferingw ith catalytic activity.M oderate yields of 32-42 % were obtained with aniline derivatives, which are challenging substrates due to their relativelyl ow nucleophilicity.B isamidation of aliphatic diamines, for example, hexane-1,6-diamine and piperazine, occurred and gave good yields of 3ae (94 %) and 3af (95 %), respectively.T he reactionw ith aromatic diamine p-phenylenediamineg ave monoamide 3ag in 45 %y ield.…”

“…Direct amidation of esters with amines represents an attractive approacht os ynthesize amides, as in most cases ac atalyst insteado fs toichiometric amountso fc ondensing reagents is used. Moreover, the only byproducts of the reactiona re alcohols, an outcome that is also superior to conventional methods in terms of green chemistry.S ystems have been developed to catalyzet his transformation,i nvolving heterogeneous catalysts, [4] inorganic salts or bases, [5][6][7][8][9][10][11] organicc atalysts [12][13][14][15][16][17] ,e nzymes, [18] and metal complexes. [19][20][21][22][23][24][25] In general,l arge loadings of catalysts (nearlys toichiometric)a re required, and substrates are mainly limited to reactive aliphatic amines such as benzylamine and hexylamine.…”